Key Takeaways
- EsoBiotec’s ESO-T01 therapy shows promise in treating multiple myeloma, with four patients participating in a phase 1 trial demonstrating positive responses.
- Two out of four patients achieved complete cancer resolution, while others experienced partial responses; all faced adverse effects including cytokine release syndrome.
- AstraZeneca’s $1 billion investment in EsoBiotec underscores the pharmaceutical giant’s commitment to innovative therapies in the CAR-T space.
Initial Phase 1 Results for EsoBiotec’s ESO-T01 Therapy
EsoBiotec has unveiled promising data from its ongoing phase 1 trial of ESO-T01, an innovative in vivo T-cell editing therapy targeting multiple myeloma. The details of the trial, presented in The Lancet on July 2, indicate that all four patients who received the treatment responded positively, with two experiencing complete resolution of their cancer. The trial, held in Wuhan, China, aims to include up to 24 patients suffering from relapsed or refractory multiple myeloma, with each participant having previously undergone at least two other treatments.
ESO-T01 utilizes lentivirus vectors to deliver mRNA directly into T cells, enabling these immune cells to better recognize and destroy cancer cells. Specifically designed to target B-cell maturation antigen (BCMA), which is often overexpressed in malignant cells associated with multiple myeloma, ESO-T01 constitutes EsoBiotec’s lead clinical asset.
Patients received a single infusion of ESO-T01, but not without experiencing varying degrees of adverse events. Reports indicated that all participants exhibited acute inflammatory reactions, including chills and fevers, on the day of the infusion. Additionally, three patients required medication for low blood pressure, and all developed cytokine release syndrome, with severity ranging from grade 1 to grade 3. The patient with the most extensive cancerous tissue also faced immune effector cell-associated neurotoxicity syndrome (ICANS).
While two patients achieved complete remission of their cancerous lesions by day 28 and two months post-infusion respectively, the remaining participants showed partial responses characterized by reduced cancer cell presence and diminished tumor lesions. The authors of the study highlighted that ESO-T01 appeared to effectively target extramedullary disease, a form of myeloma manifesting outside the bone marrow.
Despite these encouraging results, the researchers emphasized the necessity for a more extensive patient cohort and prolonged follow-up to ascertain the sustainability of the CAR T-cells produced and their long-term efficacy. The authors underscored the importance of a randomized controlled trial for substantiating these findings.
AstraZeneca’s involvement in the advancement of this area is further underscored by its $1 billion acquisition of EsoBiotec, which includes an upfront payment of $425 million, alongside potential developmental and regulatory milestones that could reach up to $575 million. This investment was catalyzed by initial data showcasing the therapy’s effectiveness from a single patient presented at the J.P. Morgan Healthcare Conference earlier this year.
Lentiviral vectors like those utilized by EsoBiotec have gained attention known for their low toxicity and capability to infect a wide range of cells, which could inform future treatment strategies. Current examples include Orchard Therapeutics’ approved therapy for metachromatic leukodystrophy, Libmeldy, and bluebird bio’s Zynteglo for sickle cell disease.
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